Combined Analysis of Network Toxicology and Metabolomics Uncovers the Potential Mechanisms Underlying Neodymium Oxide-Induced Pulmonary Fibrosis

Rare earth element-related occupational and environmental health risks have received increasing attention, but the molecular mechanisms underlying neodymium oxide (Nd2O3)-induced pulmonary fibrosis remain unclear. This study aimed to identify potential targets, metabolites, and pathways involved in fibrosis-related lung responses after Nd2O3 exposure. An integrated network toxicology and metabolomics approach was combined with an in vivo mouse model of Nd2O3-induced pulmonary toxicity. Histopathological injury, collagen deposition, and fibrosis-related protein expression were evaluated by HE staining, Masson staining, and Western blotting, respectively. Candidate targets were identified from public databases, key pathways were analyzed through network construction, and selected genes were validated by RT-qPCR. Nd2O3 exposure caused evident lung injury, inflammatory cell infiltration, structural disruption, increased collagen deposition, and elevated fibrosis-related protein expression. A total of 162 overlapping targets related to Nd2O3 exposure and pulmonary fibrosis were identified. ESR1, PTGS2, HSP90AA1, and MMP9 emerged as key targets, while cAMP signaling, arachidonic acid metabolism, PI3K-Akt signaling, and efferocytosis-related processes were implicated. Metabolomics showed distinct separation between control and high-exposure groups, with differential metabolites mainly associated with lipid metabolism and inflammation. RT-qPCR further confirmed altered expression of key genes. These findings suggest that Nd2O3 may promote fibrosis-related lung responses through inflammatory signaling, lipid metabolic disturbance, and profibrotic pathway activation.